The Effectiveness of HP and TMZ Synergism on Adult Recurrence GBM

NCT06218524 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: SEC-DRD2
• Study Type: interventional
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study of investigators indicated that TMZ can up-regulate dopamine D2 receptor (DRD2) expression, and mediates Ferroptosis inhibition and chemoresistance of GBM. The clinical data also proved that the DRD2 expression in recurrent GBM is significantly higher than that in primary GBM. Moreover, the DRD2 antagonist haloperidol can attenuate the above function of DRD2, and increase the sensitivity of GBM to the TMZ by inducing fatal autophagy and ferroptosis. In xenograft mice, the combined usage of haloperidol and Temozolomide (TMZ) can significantly inhibit tumor growth and increase overall survival. The investigators' findings have been published in Clinical cancer research. Haloperidol known as a butylbenzene antipsychotic drug, has been widely used in several kinds of mental illnesses, such as depression, schizophrenia, and Bipolar disorder. And the safe dosage of the haloperidol is clear so far. So in this study, the investigators will recruit the patients who suffered from recurrent GBM, and evaluate the effectiveness of single TMZ chemotherapy or combined with haloperidol.

Conditions

Glioblastoma Multiforme

Keywords

Chemoresistance; Autophagy; Ferropotosis; DRD2; Haloperidol

Outcome Measures

Primary Outcomes (1)

• Percentage of partial relief and complete relief

  Detected the percentage of partial relief and complete relief according to RANO criteria.

  3 months

Secondary Outcomes (2)

• Overall survival

  One year

• DRD2 expression

  One year

Other Outcomes (1)

• Adverse drug reaction of haloperidol

  One year

Study Arms (2)

TMZ single

PLACEBO COMPARATOR

Single oral Temozolomide

Drug: Temozolomide

TMZ and Haloperidol

EXPERIMENTAL

Oral Temozolomide and Haloperidol

Drug: Haloperidol Tablets; Drug: Temozolomide

Interventions

Haloperidol Tablets DRUG

Haloperidol tablet 6mg, Oral, Triple/Day

TMZ and Haloperidol

Temozolomide DRUG

Temozolomide, 150mg/kg, Oral, Once/Day, 5/28 days

TMZ and Haloperidol; TMZ single

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients
• Primary GBM underwent surgery and TMZ chemoradiotherapy, and MRI confirmed the tumor recurrence
• Without severe cardiac diseases

You may not qualify if:

• Child patients (\<18 years)
• Recurrence tumors grow fast, which needs surgery removal
• H3K27M midline glioblastoma
• Suffered with severe cardiac diseases

Sponsors & Collaborators

• Southern Medical University, China: lead

Related Publications (1)

• Shi L, Chen H, Chen K, Zhong C, Song C, Huang Y, Wang T, Chen L, Li C, Huang A, Qi S, Li H, Lu Y. The DRD2 Antagonist Haloperidol Mediates Autophagy-Induced Ferroptosis to Increase Temozolomide Sensitivity by Promoting Endoplasmic Reticulum Stress in Glioblastoma. Clin Cancer Res. 2023 Aug 15;29(16):3172-3188. doi: 10.1158/1078-0432.CCR-22-3971.

  PMID: 37249604 RESULT

Related Links

• Our study about the anti-tumor function of Haloperidol, which was published in Clinical Cancer research.

MeSH Terms

Conditions

Glioblastoma

Interventions

Haloperidol; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Butyrophenones; Ketones; Organic Chemicals; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Yuntao Lu, Ph.D

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuntao Lu, Ph.D

CONTACT

+86013632101002; lllu2000yun@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Neurosurgeon

Study Record Dates

• First Submitted: January 11, 2024
• First Posted: January 23, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): July 31, 2028
• Last Updated: January 23, 2024

Record last verified: 2024-01